TM6SF2/PNPLA3/MBOAT7 Loss-of-Function Genetic Variants Impact on NAFLD Development and Progression Both in Patients and in In Vitro Models
Miriam Longo, Marica Meroni, Erika Paolini, Veronica Erconi, Fabrizia Carli, Francesco Fortunato, Dario Ronchi, Roberto Piciotti, Silvia Sabatini, Chiara Macchi, Anna Alisi, Luca Miele, Giorgio Soardo, Giacomo P. Comi, Luca Valenti, Massimiliano Ruscica, Anna Ludovica Fracanzani, Amalia Gastaldelli, Paola Dongiovanni
Abstract
BACKGROUND & AIMS: cells. METHODS: ) through Clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9). RESULTS: cells also showed the highest proliferation rate. Finally, the re-overexpression of MBOAT7 and/or TM6SF2 reversed the metabolic and tumorigenic features observed in the compound knockout model. CONCLUSIONS: The co-presence of the 3 at-risk variants impacts the NAFLD course in both patients and experimental models, affecting LD accumulation, mitochondrial functionality, and metabolic reprogramming toward HCC.